Anandamide Regulates Postnatal Development of Long-Term Synaptic Plasticity in the Rat Dorsolateral Striatum

Abstract

Long-term changes in synaptic efficacy produced by high-frequency stimulation (HFS) of glutamatergic afferents to the rat dorsolateral striatum exhibit heterogeneity during early stages of postnatal development. Whereas HFS most often induces striatal long-term potentiation (LTP) in rats postnatal day 12 (P12)-P14, the same stimulation tends to induce long-term depression (LTD) at ages P16 -P34. Previous studies have shown that striatal LTD induction depends on retrograde endocannabinoid signaling and activation of the CB1 cannabinoid receptor. It is also known that levels of one of the primary endogenous CB1 receptor agonists, anandamide (AEA), increases during development in whole-brain samples. In the present study, we sought to determine whether this developmental increase in AEA also takes place in striatal tissue and whether increased AEA levels contribute to the postnatal switch in the response to HFS. We observed a pronounced increase in striatal levels of AEA, but not the other major endogenous cannabinoid 2-arachidonoylglycerol (2-AG), during the postnatal period characterized by the switch from LTP to LTD. Furthermore, application of synthetic AEA during HFS in field recordings of slices from P12-P14 rats allowed for induction of LTD whereas blocking the CB1 receptor during HFS in animals P16 -P34 resulted in expression of LTP. However, blocking 2-AG synthesis with the DAG-lipase inhibitor tetrahydrolipstatin did not alter HFSinduced striatal LTD. In addition, synaptic depression produced by a synthetic CB1 agonist was similar across development. Together, these findings suggest that the robust developmental increase in striatal AEA may be the key factor in the emergence of HFS-induced striatal LTD.

Combined Activation of L-Type Ca2+ Channels and Synaptic Transmission Is Sufficient to Induce Striatal Long-Term Depression

“…Because FPL-LTD was induced during blockade of PLC with U73122, our data suggest that the dependence of PLC activation becomes redundant during periods of high postsynaptic [Ca 2ϩ ] i , because endocannabinoid production may be stimulated sufficiently by calcium alone (Chevaleyre et al, 2006). Recent studies have suggested that the endocannabinoid anandamide participates in the induction of striatal LTD (Ade and Lovinger, 2007;Kreitzer and Malenka, 2007). Anandamide synthesis can be stimulated by increased intracellular calcium via molecular steps that do not involve PLC (Di Marzo et al, 1994).…”

“…The strategic position of Ca v 1.3 thus may be crucial for efficient activation of Ca 2ϩ -dependent modulatory cascades involved in LTD induction (Olson et al, 2005). The 2-arachidonoylglycerol (2-AG) synthetic enzyme diacylglycerol lipase also is located in the perisynaptic region of MSN dendritic spines near mGluR5 (Uchigashima et al, 2007), although it must be noted that the role of 2-AG in LTD is still unclear (Ade and Lovinger, 2007;Kreitzer and Malenka, 2007). Thus Ca v 1.3 may be part of a signaling com- Figure 5.…”

Differential Tonic GABA Conductances in Striatal Medium Spiny Neurons

“…In some experiments, the glutamatergic afferents were stimulated by square-wave 50 s electric pulses delivered by a bipolar stimulating electrode placed within the white matter at the corticostriatal border as in the study by Ade and Lovinger (2007) at a frequency of 0.2 Hz. Action potential firing was recorded from single cells in loose cell-attached configuration.…”

Distinct Functional and Anatomical Architecture of the Endocannabinoid System in the Auditory Brainstem

“…In the hippocampus (Chevaleyre et al 2006;Hashimotodani et al 1997a;Katona et al 2006;Makara et al 2005), cerebellum (Safo and Regehr 2005;Szabo et al 2006;Yoshida et al 2006), striatum (Uchigashima et al 2007), and prefrontal cortex (Lafourcade et al 2007;Melis et al 2004), 2-AG is the most common EC mediating short-and long-term plasticity. However, AEA is involved in EC-dependent LTD in amygdala and the levels of AEA determine the sign of synaptic plasticity in the striatum (Ade and Lovinger 2007;Azad et al 2004). Given the similarities of the DCN with the cerebellum (Oertel and Young 2004), we focused initially on 2-AG.…”